(26 days)
Intended for use with the TAS analyzer and TAB LHMT cards to provide a method for quality control of the system.
The controls for TAS LHMT cards consist of two separate vials. One was designed to mimic a sample from a normal individual, and the second to mimic a sample from a patient with a prolonged clotting time due to administration of heparin. These controls are made with pig plasma. To make the controls as easy to use as possible for point-of-care testing, we chose the patented packaging system of Medtox, (Burlington, NC). This consists of a closed, crushable glass ampoule containing lyophilized plasma which is inside a plastic sleeve. The sleeve contains water for diluent and has a capped dropper top with a filter in the tip (to remove glass shards from the sample). The entire assembly is shrink wrapped with a label and plastic seal. To use, the ampoule is crushed inside the plastic sleeve, which allows the diluent to mix with the Ivophilized plasma. The mixture is reconstituted by shaking or vortexing the capped vial. The plastic seal and cap are removed and three drops of plasma suspension are discarded into a biohazard waste container (to eliminate the dilution effect of the diluent that is contained in the filter). A drop of the plasma suspension is added to a TAS LHMT card in an analyzer. The rest of the test procedure and the manner of signal production is identical to that for a patient sample.
The provided text describes the TAS LHMT Controls, a device used for quality control of the TAS Analyzer and TAS LHMT cards in coagulation studies.
Here's an analysis of the acceptance criteria and the study that demonstrates device performance:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state formal "acceptance criteria" or specific thresholds the device must meet for approval. Instead, it demonstrates the device's performance through precision studies. The primary goal is to show that the TAS LHMT Controls perform "comparably" and are "substantially equivalent" to the predicate device (TAS HMT controls) and produce consistent clotting times within expected ranges.
Therefore, the "acceptance criteria" are implicitly derived from the reported precision (low CV%) for both normal and heparin controls, and the demonstration that the control produces clotting times "like that of a normal individual" and "mimics the response of a patient given a moderate level of heparin." The stability data (room temperature and freezer stability) also functions as a performance measure.
| Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance (TAS LHMT Controls) |
|---|---|---|
| Within-day Precision | Low Coefficient of Variation (CV%) for clotting times | Normal Control: Mean 151 sec, SD 1.7, CV 1.1% |
| Heparin Control: Mean 296 sec, SD 9.8, CV 3.3% | ||
| Lot-to-lot Precision | Low Coefficient of Variation (CV%) across different lots | Normal Control (3 lots): Mean 152-153 sec, CV 1.0-2.3% |
| Heparin Control (3 lots): Mean 293-296 sec, CV 3.7-5.7% | ||
| Mimicry of physiological states | Normal control produces clotting time like a normal individual; Heparin control mimics a patient with moderate heparin. | Normal control produced clotting time "like that of a normal individual"; Heparin control "mimics the response of a patient given a moderate level of heparin." |
| Stability (Room Temp) | Stable for a specified period (e.g., at least 6 weeks) | Stable for at least 6 weeks at 20-25°C indicating probable refrigerator stability of at least six months. |
| Stability (Reconstituted) | Stable for a specified short period | Reconstituted vials are stable for five minutes. |
| Stability (Freezing) | Little to no effect on performance | No significant difference in mean or CV produced by controls stored at -80°C compared to refrigerated vials. |
| Effect of Heating | Avoid significant increase in clotting time | Heating intact vials to 37°C for several days causes an increase in mean clotting time. (This is a condition to avoid, not a criterion to meet, showing understanding of limits). |
| Dispensing Angle | Little to no effect on results | Little effect on mean clotting times or CV. |
2. Sample size used for the test set and the data provenance
- Sample Size for Precision Studies:
- Within-day precision: The sample size (n) for the within-day precision is not explicitly stated in the provided table. It gives a single mean, SD, and CV, suggesting multiple measurements were taken to derive these metrics.
- For Lot-to-lot precision: "n = 30 each" is stated, meaning 30 measurements were taken for each of the three lots for both the Normal and Heparin controls. So, 30 measurements for Normal Lot 1, 30 for Normal Lot 2, 30 for Normal Lot 3, and similarly for the Heparin lots.
- Data Provenance: The document does not specify the country of origin of the data. The studies appear to be retrospective analyses, conducted by the manufacturer, Cardiovascular Diagnostic, Inc., to characterize the performance of their TAS LHMT Controls.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable to this submission. The device (TAS LHMT Controls) is a quality control material intended to verify the proper functioning of an analyzer and test cards. Its "ground truth" is its inherent chemical and physical properties that, when measured by the TAS system, produce expected clotting times. There are no human "experts" establishing a diagnostic ground truth for individual cases. The "ground truth" for the controls themselves (e.g., what constitutes a "normal" clotting time or a "heparinized" clotting time) is established by the design of the control material to mimic these states.
4. Adjudication method for the test set
This information is not applicable. Since this device is a quality control material, there is no need for expert adjudication of results, as there would be for a diagnostic device interpreting patient samples. The measurements are objective clotting times from the control material.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This information is not applicable. This device is a quality control reagent, not an AI-assisted diagnostic tool. Therefore, MRMC studies and the concept of "human readers improving with AI" do not apply.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This information is not applicable. The device is a control material, not an algorithm. Its performance is measured through its objective chemical properties and the reproducibility of results obtained from the measurement system it is designed to control.
7. The type of ground truth used
The "ground truth" for the TAS LHMT Controls are:
- Designed chemical properties: The controls are made with pig plasma and formulated to produce specific clotting times under defined conditions.
- Mimicry of physiological states: The "Normal" control is designed to produce a clotting time similar to a normal individual, and the "Heparin" control is designed to mimic a patient with a moderate level of heparin. This is the intended performance characteristic that the control aims to represent.
- Comparison to predicate device: The performance is also validated by comparing it to the predicate TAS HMT controls, ensuring "no significant differences" in performance.
8. The sample size for the training set
This information is not applicable. This is a quality control reagent, not a machine learning or AI-based device that requires a "training set." The controls are manufactured based on established chemical formulations and tested for consistency and performance.
9. How the ground truth for the training set was established
This information is not applicable for the same reasons as #8.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.